Nov. 8, 2022

 

NIPM Fall Seminar (Virtual) Artem Barski, Ph. D. Associate Professor | University of Cincinnati Nov. 10, 2022 at 12 pm 

Abstract provided by Dr. Artem Barski:

Epigenomics of T cell memory

The research area of my laboratory is epigenetics. We use computational and experimental tools, such as Scientific Data Analysis Platform (https://SciDAP.com) we developed for analysis of omics data, to explore epigenetic and transcriptional regulation in various systems, but the main focus of the lab is the regulation of adaptive immune response. The key feature of adaptive immunity is the rapid recall response of memory T cells: the ability of memory T cells to produce cytokines in response to pathogen much more rapidly than naïve T cells. We recently found that this rapid recall ability is associated with epigenetic gene poising. Here, we aim to uncover the mechanism that underlie chromatin remodeling during initial activation of T cells and, thus, contribute to the establishment of memory phenotype. Upon encountering an antigen, naïve T helper cells become activated, differentiate into several lineages and contribute to immune response. Activation of T cells is dependent on organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naïve T cells within hours of activation. These newly open regions were strongly enriched for the AP-1 motif, and indeed, ChIP-seq demonstrated AP-1 binding at more than 70% of them. Broad inhibition of AP-1 activity prevented chromatin opening at AP-1 sites and reduced expression of nearby genes. Similarly, induction of anergy in the absence of co- stimulation during activation, was associated with reduced induction of AP-1 and a failure of proper chromatin remodeling. The translational relevance of these findings was highlighted by the substantial overlap of AP-1–dependent elements with risk loci for multiple immune diseases, most notably multiple sclerosis, IBD and allergy. Our findings define AP-1 as the key link between T cell activation and chromatin remodeling.

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